title: Absence of mutations in the analysis of coding sequences of the entire transforming growth factor-beta type II receptor gene in sporadic human breast cancers.
abstract: The transforming growth factor-beta (TGFbeta) binds the type II TGFbeta growth factor receptor (TGFbetaRII) to inhibit the growth of most epithelial tissues. Most human colon and gastric cancers with microsatellite instability (MI) have frameshift mutations in polynucleotide repeats within the TGFbetaRII coding region; these mutations truncate the receptor protein and disable the serine/threonine kinase to produce TGF-beta resistance. To further investigate the type, frequency and tissue distribution of TGFbetaRII gene mutations, in this study, we examined 36 sporadic breast cancers. We previously produced eight intron based primer pairs for mutational analysis of the entire coding region of the TGFbetaRII gene. Using these primers, we developed protocols for polymerase chain reaction-single strand conformational polymorphism (PCR-SSCP) analysis of PCR products from genomic DNA samples of 36 breast cancer patients and we tested them for microsatellite instability (MI) at eight microsatellite loci. One case demonstrated MI (2.8%) and we found no mutations. These and other recent data indicate that TGFbetaRII mutations are essentially confined to colon and gastric cancers with MI. The narrow spectrum of tissues containing RII mutations illustrates the complexity of genetic checkpoints in human carcinogenesis.
authors.affiliation: First Department of Surgery, Gunma University School of Medicine, 3-39-22, Showa-machi, Maebashi, Gunma, 371, Japan.
authors.forename: S
authors.initials: S
authors.lastname: Takenoshita
authors.forename: A
authors.initials: A
authors.lastname: Mogi
authors.forename: M
authors.initials: M
authors.lastname: Tani
authors.forename: H
authors.initials: H
authors.lastname: Osawa
authors.forename: H
authors.initials: H
authors.lastname: Sunaga
authors.forename: H
authors.initials: H
authors.lastname: Kakegawa
authors.forename: Y
authors.initials: Y
authors.lastname: Yanagita
authors.forename: T
authors.initials: T
authors.lastname: Koida
authors.forename: M
authors.initials: M
authors.lastname: Kimura
authors.forename: K I
authors.initials: KI
authors.lastname: Fujita
authors.forename: H
authors.initials: H
authors.lastname: Kato
authors.forename: R
authors.initials: R
authors.lastname: Kato
authors.forename: Y
authors.initials: Y
authors.lastname: Nagamachi
mesh_terms: D001483:Base Sequence; D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology; D002277:Carcinoma / Q000235:genetics* / Q000473:pathology; D004252:DNA Mutational Analysis; D017931:DNA Primers / Q000737:chemistry; D004273:DNA, Neoplasm / Q000032:analysis; D004276:DNA, Satellite / Q000235:genetics; D005260:Female; D006801:Humans; D018895:Microsatellite Repeats; D008969:Molecular Sequence Data; D009154:Mutation; D016133:Polymerase Chain Reaction; D018807:Polymorphism, Single-Stranded Conformational; D017346:Protein Serine-Threonine Kinases; D000077294:Receptor, Transforming Growth Factor-beta Type II; D018125:Receptors, Transforming Growth Factor beta / Q000235:genetics*; D016212:Transforming Growth Factor beta / Q000235:genetics*
chemical_list: D017931:DNA Primers; D004273:DNA, Neoplasm; D004276:DNA, Satellite; D018125:Receptors, Transforming Growth Factor beta; D016212:Transforming Growth Factor beta; D017346:Protein Serine-Threonine Kinases; D000077294:Receptor, Transforming Growth Factor-beta Type II